The proline analogue azetidine-2-carboxylic acid (AzC) induces drastic alterations in the pattern of gene expression in HeLa cell cultures. Synthesis of the majority of normal cell proteins is depressed whereas the production of a characteristic set of about 5 polypeptides is induced. Upon prolonged exposure, some of the AzC-induced proteins become major constituents of the cell. Various other cell types exhibit similar responses to alternative stimuli of diverse nature. We propose: 1) to elucidate the nature and properties of the AzC-induced proteins, to determine their relationships to one another, to normal cell proteins and to the proteins induced by other stimuli. In addition, antibodies directed against the induced proteins will be prepared. 2) to investigate the alterations in RNA metabolism which accompany induction and deinduction to discover the fate of preexisting mRNAs and to characterize the induced mRNAs. 3) to prepare cloned copies of the mRNAs coding for the induced proteins and use these to probe the structure of their genes and the mechanism of induction. 4) to analyse the induction mechanism using selective inhibitors of macromolecular synthesis specific probes and cell-free protein synthesizing systems. 5) to further investigate the response to AzC using cell mutants which are resistant to the inducing effects of AzC.